Method for producing Ac-225 by irradiation of Ra-226 with protons

ABSTRACT

This invention refers to a method for producing Actinium-225, comprising the steps of preparing a target ( 1 ) containing Radium-226, of irradiating this target with protons in a cyclotron and of chemically separating Actinium from the irradiated target material thereafter. According to the invention the proton energy in the cyclotron is adjusted such that the energy incident on the Ra-226 is between 10 and 20 MeV, preferably between 9 14 and 17 MeV. By this means the yield of production of the desired isotope Ac-225 is enhanced with respect to other radioisotopes.

The invention refers to a method for producing Ac-225, comprising thesteps of preparing a target containing Ra-226, of irradiating thistarget with protons in a cyclo-tron and of chemically separating Ac fromthe irradiated target material. Such a method is known for example fromEP-A-0 752 709.

According to this document the protons are accelerated in a cyclotronand are projected onto a target containing Ra-226 so that unstableradionuclei are transformed into Actinium by emitting neutrons. Thepossible nuclear reactions lead among others to Ac-226, Ac-225 andAc-224.

Radio-immunotherapeutic methods for locally attacking cancer disease(metastases) become more and more important in view of progresses inimmunology and radiotherapy and in the molecular biology field.Generally speaking, short half-life alpha-emitting nuclides areconjugated to a carrier (e.g. monoclonal antibodies) which after havingbeen introduced into the patient body tend to be linked to and beintegrated into malign cells and to destroy these cells due to anintense irradiation of very short range. The radionuclide must in thiscase cope with particular requirements: It must be apt to be linked forconjugation to a convenient antibody, it must have a convenienthalf-life and it should be readily available.

Among the possible candidates for such a radionuclide, Ac-225 and itsdaughter Bismuth-213 are preferred for radio-immunotherapy purposes (seefor example EP-B-0 473 479). In the above cited document EP-A-0 752 709it is described that the irradiation of Ra-226 by a proton beam resultsin the desired Ac-225 but also in considerable quantities of otherhighly undesired radionuclides, especially Ac-224 and Ac-226. In orderto eliminate these undesired radionuclides said document suggests todelay the post-irradiation processing since the undesired nuclides citedabove present a fairly short half-life compared with Ac-225 (half-life10 days). Nevertheless this waiting period also leads to a considerableloss of Ac-225.

The invention proposes a method allowing to reduce or even eliminatethis waiting period by a method supplying a higher yield and purity ofthe produced Ac-225. A further object of the invention is to produceAc-225 by observing the safety regulations for handling the basic veryradiotoxic material Ra-226 and the purity specifications of Ac-225 asrequired for the therapeutic use.

These objects are achieved by the method as claimed in claim 1. It hasbeen found that the highest purity is achieved at an intermediate valueof the proton impact energy of about 15 Mev.

Further improvements of the method as far as the preparation of thetarget, its irradiation and its final processing is concerned, arespecified in the secondary claims.

The invention will now be described in more detail by means of apreferred embodiment and with reference to the enclosed drawings whichshow schematically a target assembly prepared to receive a proton beamfrom a cyclotron source.

The target nuclide is Ra-226 in the chemical form of RaCl₂(Radiumchloride), obtained from precipitation with concentrated HCl, orradium carbonate RaCO₃. This material is then pressed in target pellets1. Prior to irradiation these pellets are heated to above 150° C. inorder to release crystal water therefrom before being sealed in acapsule 2 made of silver. The capsule is then mounted on a frame-likesupport 3 of a two-part casing 4 held together by screws 10. The capsuleis surrounded by a cooling space connected to an outer water coolingcircuit 6. This outer circuit comprises a circulation pump 7 and a heatexchanger 8 for extracting the heat produced during irradiation in thecapsule. The proton beam passes through a window 9 which is disposed inthe wall of the casing 4 in face of the target 1. The square surfacearea of the target 1 which is hit by the beam may be for example about 1cm².

It has been found that the distribution of the different producedActinium isotopes depends largely upon the impact energy of the protonson the radium target nuclei. Table 1 shows experimental data on theproduction of different relevant radionuclides under irradiation ofRa-226 for 7 hours with a proton beam (10 μA) of variable impact energy.In this table the ratio Ra-224/Ra-226 is given instead of the ratioAc-224/Ra-226. However Ra-224 is a daughter product of Ac-224 the latterhaving a short half-life of only 2.9 hours. This daughter product isparticularly undesirable because one of its daughters is a gaseous alphaemitter (Rn-220) and another daughter Tl-208 is a high energy gammaemitter (2.615 MeV).

This table shows that the highest yield in Ac-225 is obtained at anintermediate value of the impact energy, globally situated between 10and 20 MeV and preferably between 14 and 17 MeV. Of course, the protoncurrent is adjusted as high as possible depending upon the cyclotroncapability and the maximum heat load which can be carried away by thecooling circuit 6.

After irradiation, the target 1 is dissolved and then treated in aconventional way in order to separate Ac from Ra, for example inion-exchangers.

The choice of silver for the capsule material is preferred for its highthermal conductivity which allows an efficient heat extraction, and forits inert chemical nature. The capsule provides a leak-tight seal forthe highly radiotoxic material Ra-226, allows target processing afterirradiation without introducing impurities into the medical gradeproduct and avoids the introduction of unwanted cations which wouldinterfere with the chelation of the radionuclides. Interactions betweenthe target material and the silver capsule will not occur.

It is nevertheless advisable to monitor the leak-tightness in thecooling circuit 6 by an alpha monitor 11. Preferably an alpha-tightouter containment (not shown) surrounds the casing 4 and may furthercontain Radon traps.

TABLE 1 Yield of the relevant isotope (in activity percent with respectto Ra-226) Energy of protons ²²⁵Ra/²²⁶Ra ²²⁴Ra/²²⁶Ra ²²⁵Ac/²²⁶Ra²²⁶Ac/²²⁶Ra incident reaction: reaction: reaction: reaction: on ²²⁶Rap,pn p,3n p,2n p,n (MeV) (activ %) (activ %) (activ %) (activ %) 24.52.19 22 0.85 20.1 1.09 47 4.55 2.1 15.2 0.22 4.5 15.00 10.4 0.02 0 5.000 5.5 0.02 0 0.05 0

What is claimed is:
 1. A method for producing Actinium-225, comprising the steps of preparing a target (1) containing Radium-226, of irradiating this target with protons in a cyclotron and of chemically separating Actinium from the irradiated target material, wherein the proton energy in the cyclotron is adjusted such that the energy incident on the Ra-226 is between 10 and 20 MeV.
 2. A method according to claim 1, wherein the proton energy is adjusted such that the energy incident on the Ra-226 is between 14 and 17 MeV.
 3. A method according to claim 1, wherein the target (1) consists of compressed pellets mainly made of radium chloride RaCl₂ or from radium carbonate RaCO₃.
 4. A method according to claim 3, wherein the preparation of the target includes a step of heating the target material to a temperature above 150° C., in order to remove crystalline water.
 5. A method according to claim 1, wherein in view of the irradiation, the target (1) is tightly sealed in a capsule (2) made of silver, this capsule being itself associated to a closed coolant fluid circuit (6).
 6. A method according to claim 5, wherein the closed coolant fluid circuit (6) is equipped with an alpha monitor (11).
 7. A method according to claim 5, wherein the capsule (2) and a casing (4) in which it is inclosed are installed in an alpha-tight cell.
 8. A method according to claim 7, wherein the alpha-tight cell is equipped with a biological shielding and with radon traps. 